US4599229A - Method of promoting animal growth using antibodies against somatostatin - Google Patents

Method of promoting animal growth using antibodies against somatostatin Download PDF

Info

Publication number
US4599229A
US4599229A US06/773,814 US77381485A US4599229A US 4599229 A US4599229 A US 4599229A US 77381485 A US77381485 A US 77381485A US 4599229 A US4599229 A US 4599229A
Authority
US
United States
Prior art keywords
antibodies
animal
growth
somatostatin
administered
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US06/773,814
Inventor
Maria-Luisa Maccecchini
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
International Minerals and Chemical Corp
Intervet Inc
Original Assignee
International Minerals and Chemical Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by International Minerals and Chemical Corp filed Critical International Minerals and Chemical Corp
Priority to US06/773,814 priority Critical patent/US4599229A/en
Assigned to INTERNATIONAL MINERALS & CHEMICAL CORPORATION, A CORP OF NEW YORK reassignment INTERNATIONAL MINERALS & CHEMICAL CORPORATION, A CORP OF NEW YORK ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: MACCECCHINI, MARIA-LUISA
Priority to DE86305234T priority patent/DE3684211D1/de
Priority to EP86305234A priority patent/EP0216454B1/en
Priority to JP61158087A priority patent/JPS6270321A/en
Priority to AT86305234T priority patent/ATE73350T1/en
Application granted granted Critical
Publication of US4599229A publication Critical patent/US4599229A/en
Assigned to SCHERING-PLOUGH ANIMAL HEALTH CORPORATION reassignment SCHERING-PLOUGH ANIMAL HEALTH CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MALLINCKRODT, INC.
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A23K20/147—Polymeric derivatives, e.g. peptides or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/809—Drug, bio-affecting and body treating compositions involving immunoglobulin or antibody fragment, e.g. fab', fv, fc, heavy chain or light chain
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/866—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain

Definitions

  • This invention relates to a method of enhancing the growth rate of animals. More specifically, this invention relates to enhancing animal growth rate by passively immunizing them with monoclonal or polyclonal antibodies against somatostatin.
  • Somatostatin or somatotropin release-inhibiting factor is an antagonist of growth hormone releasing factor (GHRF) and is believed to interfere with growth by inhibiting growth hormone (GH) secretion.
  • GHRF growth hormone releasing factor
  • a method for enhancing the rate of growth in animals involves administering to the animals growth-enhancing amounts of anti-somatostatin monoclonal or polyclonal antibodies.
  • FIG. 1 is a graph illustrating the growth curve (mean weights) of rats which had been administered different amounts of heterologous antibody fragments specific for somatostatin.
  • FIG. 2 is a graph illustrating changes in blood urea nitrogen levels of the same groups of rats during the period they were treated with the antibody fragments.
  • the present invention relates to a method for enhancing the rate of growth in animals. More specifically, the invention relates to a method of enhancing growth rate by administering to the animals growth enhancing amounts of monoclonal or polyclonal antibodies specific for somatostatin obtained from the same species or different species of animal.
  • monoclonal or polyclonal antibodies specific for somatostatin obtained from the same species or different species of animal.
  • homologous antibodies i.e., antibodies derived from the same animal species as that to be treated
  • whole antibodies or antibody fragments may be administered.
  • the antibodies are obtained from a heterologous source (i.e., the antibodies are derived from a different animal species than the species being treated), preferably antibody fragments, rather than whole antibodies, are administered.
  • the antibodies used in the method of this invention are generally obtained using conventional techniques.
  • Somatostatin is isolated, purified and coupled to a carrier protein.
  • a carrier protein typically, immunization of animals with an endogenous substance does not lead to antibody production against that substance.
  • somatostatin in this instance, to an exogenous, carrier protein, a protein hybrid is formed which can be used as an antigen to elicit the desired immune response.
  • carrier proteins can be linked to the somatostatin, including albumin, serum albumin, thyroglobulin, and ⁇ -globulin.
  • Polyclonal antibodies may be obtained in accordance with conventional procedures.
  • An animal such as a rabbit, is infected a number of times over a period of, typically, a few weeks with the somatostatin-carrier protein hybrid. Blood samples containing the anti-somatostatin antibodies then are extracted from the animal.
  • the techniques for making monoclonal antibodies also are well known and are taught by U.S. Pat. No. 4,172,124 (1979), issued to Koprowski and incorporated herein by reference.
  • the somatostatin and carrier protein are cross-linked with a cross-linker such as glutaraldehyde and injected intraperitoneally into an animal with immune response capability, preferably a mouse or a rat.
  • Most of the antibodies formed are directed against the carrier protein; only a few are directed against the somatostatin.
  • Spleenic lymphocytes are removed from the animals and screened for antibodies having a high specificity and affinity for somatostatin. The desired lymphocytes are suspended in a non-lethal medium.
  • the myeloma cells preferably are of the same species as the injected animal.
  • the myeloma cells and lymphocytes are combined under cell-fusing conditions to produce the desired hybridomas.
  • the hybridoma cells are separated from unfused cells by placing the cell mixture in a medium which selectively kills the unfused myeloma cells and fused myeloma homokaryons but allows the hybridomas to survive. Standard commercial media can be used for this step.
  • the unfused lymphocytes have a finite lifespan in vitro and naturally die, whereas the hybridoma cells reproduce indefinitely in a nutrient medium under cell growth conditions.
  • the monoclonal antibodies may be produced in vitro or in vivo using well-known methods. In vitro culturing of the hybridoma cells in a nutrient medium results in secretion of antibodies into the medium.
  • the supernatants of mature hybridoma cell cultures are tested for the presence of antibodies which selectively bind to somatostatin using conventional methods such as ELISA (enzyme linked immunosorbent assay).
  • Cultures producing the desired antibodies are selected and subsequently cloned and characterized.
  • the desired cell lines then may be cultured using conventional techniques. Samples may be frozen in liquid nitrogen for future use.
  • the anti-somatostatin animal antiserum can be purified by conventional means, such as ammonium sulfate precipitation and sepharose affinity chromatography. If desired, the purified anti-somatostatin immunoglobulins then can be digested with papain and the digest purified on a second column to yield anti-somatostatin Fab' fragments. If the animal from which the antibodies were obtained is of the same species as that which is to be immunized, either whole monoclonal or polyclonal antibodies or the Fab' fragments thereof may be administered. If, on the other hand, the antibodies are obtained from a heterologous animal species, it has been found that the Fab' fragments are more effective than the whole antibody in enhancing animal growth rate. It is theorized that when the whole heterologous antibody is administered to an animal, the antibody stimulates its own immune response and is inactivated. There is a much lower chance of this occurring when the animal is immunized with Fab' fragments.
  • the antibodies can be administered to animals in one of several ways.
  • One easy and convenient method is to package a growth enhancing amount of the antibodies or antibody fragments into a slow-release delivery device and implant the device into the animal.
  • the delivery device may be in the form of either a reservoir or a matrix system.
  • Matrix and reservoir systems are well known in the art as implant devices and such systems comprising the antibodies useful in the method of this invention can be constructed in accordance with conventional techniques.
  • the antibodies also can be administered by means of an infusion pump, such as those manufactured by Alza Corporation.
  • the animals can be injected with a solution, such as a saline solution, containing a growth enhancing amount of the antibodies or antibody fragments.
  • the quantity of antibody preparation necessary to inhibit the action of somatostatin and, therefore, enhance growth rate varies with the animal species.
  • One skilled in the art can readily determine optimum dosage ranges in target animal species by conducting standard dose titration experiments. For example, it has been found that a dose of approximately 10 to 20 ⁇ g of antibody per day is sufficient to lower somatostatin levels in 100-300 gram rats and show approximately 10-15% growth enhancement over other rats of similar weight which received saline injections.
  • Anti-somatostatin IgG antibodies derived from rabbits were obtained from Purification Engineering, Inc. The antibodies were digested by papain, and the digest repurified on an S-Sepharose 4B affinity column. A total of 5.4 mg anti-S Fab' fragments were obtained (135 ml. 40 ⁇ g/ml of Fab').
  • the rats of each group were housed in a colony cage measuring 26" ⁇ 20" ⁇ 7" during the 8 week trial.
  • the mean weights were taken at two-week intervals of all the rats present in each group.
  • five rats were sacrificed from each group every two weeks on the weighing day. Therefore, the number of rats represented by the mean varied from 20 rats at days 0 and 14 to 5 rats at day 56. All rats were fed standard laboratory rat chow and water, both ad lib. Lighting conditions were 16 hours of light and 8 hours of dark. The temperature fluctuated with ambient temperature (approximately 20° C.). Table A below shows the results of the mean weights.
  • FIG. 1 shows the growth curve (mean weights) for the different groups.
  • the percentage weight gain of the high Fab' group compared to the saline control group is listed in Table B below.
  • FIG. 2 shows the mean blood urea-nitrogen levels for the different groups. As shown in FIG. 2, the BUN levels measured in the experimental and control groups supported the weight data. The group injected with high Fab' fragments showed significantly lower BUN levels than the other groups.
  • an increased growth rate is achieved in various species of birds and mammals, when they are administered growth promoting amounts of monoclonal and polyclonal Fab' fragments and whole antibodies from homologous species and monoclonal and polyclonal Fab' fragments from heterologous species.

Abstract

A method of enhancing the growth rate of animals comprises passively immunizing them with growth-enhancing amounts of anti-somatostatin antibodies.

Description

TECHNICAL FIELD
This invention relates to a method of enhancing the growth rate of animals. More specifically, this invention relates to enhancing animal growth rate by passively immunizing them with monoclonal or polyclonal antibodies against somatostatin.
BACKGROUND OF THE INVENTION
Somatostatin or somatotropin release-inhibiting factor is an antagonist of growth hormone releasing factor (GHRF) and is believed to interfere with growth by inhibiting growth hormone (GH) secretion.
Scientists have theorized that if somatostatin (S) does inhibit growth hormone secretion, manipulation of its levels may affect growth rate and body composition of animals bred for meat production. Literature reports of efforts to accomplish animal weight gain by auto-immunization, however, have been inconsistent. For example, Spencer and Williams reported auto-immunizing lambs with somatostatin linked to a carrier protein. The auto-immunized lambs gained weight more rapidly than did the control lambs; averaging 135% of the weight of the control lambs after nine weeks of treatment. Plasma somatomedin levels showed a five fold increase over the control levels; however, neither growth hormone levels nor insulin levels increased (Animal Production 32:376 (1981); Veterinary Record, p. 484, (May 22, 1984). In similar tests, Varner et al. reported that baseline and overall serum growth hormone concentrations were higher in anti-somatostatin (anti-S) auto-immunized lambs than in controls (Endocrinology 106:1027 (1980)). Despite this, Varner found that the immunized lambs gained significantly less weight than did control animals.
Thus, literature results on weight gain through active immunization are discrepant. It therefore is an object of this invention to develop a reproducible method for enhancing animal growth rates.
SUMMARY OF THE INVENTION
In accordance with the present invention, a method for enhancing the rate of growth in animals involves administering to the animals growth-enhancing amounts of anti-somatostatin monoclonal or polyclonal antibodies.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph illustrating the growth curve (mean weights) of rats which had been administered different amounts of heterologous antibody fragments specific for somatostatin.
FIG. 2 is a graph illustrating changes in blood urea nitrogen levels of the same groups of rats during the period they were treated with the antibody fragments.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a method for enhancing the rate of growth in animals. More specifically, the invention relates to a method of enhancing growth rate by administering to the animals growth enhancing amounts of monoclonal or polyclonal antibodies specific for somatostatin obtained from the same species or different species of animal. As described in greater detail below, if homologous antibodies (i.e., antibodies derived from the same animal species as that to be treated) are used, either whole antibodies or antibody fragments may be administered. If the antibodies are obtained from a heterologous source (i.e., the antibodies are derived from a different animal species than the species being treated), preferably antibody fragments, rather than whole antibodies, are administered.
The antibodies used in the method of this invention are generally obtained using conventional techniques. Somatostatin is isolated, purified and coupled to a carrier protein. Typically, immunization of animals with an endogenous substance does not lead to antibody production against that substance. By coupling the endogenous protein, somatostatin in this instance, to an exogenous, carrier protein, a protein hybrid is formed which can be used as an antigen to elicit the desired immune response. A variety of carrier proteins can be linked to the somatostatin, including albumin, serum albumin, thyroglobulin, and δ-globulin.
Polyclonal antibodies may be obtained in accordance with conventional procedures. An animal, such as a rabbit, is infected a number of times over a period of, typically, a few weeks with the somatostatin-carrier protein hybrid. Blood samples containing the anti-somatostatin antibodies then are extracted from the animal.
The techniques for making monoclonal antibodies also are well known and are taught by U.S. Pat. No. 4,172,124 (1979), issued to Koprowski and incorporated herein by reference. Typically, the somatostatin and carrier protein are cross-linked with a cross-linker such as glutaraldehyde and injected intraperitoneally into an animal with immune response capability, preferably a mouse or a rat. Most of the antibodies formed are directed against the carrier protein; only a few are directed against the somatostatin. Spleenic lymphocytes are removed from the animals and screened for antibodies having a high specificity and affinity for somatostatin. The desired lymphocytes are suspended in a non-lethal medium.
Animal myeloma cells capable of being fused to lymphocytes from the injected animal then are mixed with the lymphocytes. The myeloma cells preferably are of the same species as the injected animal. The myeloma cells and lymphocytes are combined under cell-fusing conditions to produce the desired hybridomas.
The hybridoma cells are separated from unfused cells by placing the cell mixture in a medium which selectively kills the unfused myeloma cells and fused myeloma homokaryons but allows the hybridomas to survive. Standard commercial media can be used for this step. The unfused lymphocytes have a finite lifespan in vitro and naturally die, whereas the hybridoma cells reproduce indefinitely in a nutrient medium under cell growth conditions.
The monoclonal antibodies may be produced in vitro or in vivo using well-known methods. In vitro culturing of the hybridoma cells in a nutrient medium results in secretion of antibodies into the medium.
The supernatants of mature hybridoma cell cultures are tested for the presence of antibodies which selectively bind to somatostatin using conventional methods such as ELISA (enzyme linked immunosorbent assay). Cultures producing the desired antibodies are selected and subsequently cloned and characterized. The desired cell lines then may be cultured using conventional techniques. Samples may be frozen in liquid nitrogen for future use.
The anti-somatostatin animal antiserum can be purified by conventional means, such as ammonium sulfate precipitation and sepharose affinity chromatography. If desired, the purified anti-somatostatin immunoglobulins then can be digested with papain and the digest purified on a second column to yield anti-somatostatin Fab' fragments. If the animal from which the antibodies were obtained is of the same species as that which is to be immunized, either whole monoclonal or polyclonal antibodies or the Fab' fragments thereof may be administered. If, on the other hand, the antibodies are obtained from a heterologous animal species, it has been found that the Fab' fragments are more effective than the whole antibody in enhancing animal growth rate. It is theorized that when the whole heterologous antibody is administered to an animal, the antibody stimulates its own immune response and is inactivated. There is a much lower chance of this occurring when the animal is immunized with Fab' fragments.
The antibodies can be administered to animals in one of several ways. One easy and convenient method is to package a growth enhancing amount of the antibodies or antibody fragments into a slow-release delivery device and implant the device into the animal. The delivery device may be in the form of either a reservoir or a matrix system. Matrix and reservoir systems are well known in the art as implant devices and such systems comprising the antibodies useful in the method of this invention can be constructed in accordance with conventional techniques. The antibodies also can be administered by means of an infusion pump, such as those manufactured by Alza Corporation. Alternatively, the animals can be injected with a solution, such as a saline solution, containing a growth enhancing amount of the antibodies or antibody fragments.
The quantity of antibody preparation necessary to inhibit the action of somatostatin and, therefore, enhance growth rate varies with the animal species. One skilled in the art can readily determine optimum dosage ranges in target animal species by conducting standard dose titration experiments. For example, it has been found that a dose of approximately 10 to 20 μg of antibody per day is sufficient to lower somatostatin levels in 100-300 gram rats and show approximately 10-15% growth enhancement over other rats of similar weight which received saline injections.
The present invention is illustrated by the following example, which is not to be construed as limiting.
EXAMPLE Growth Promoting Activity of Anti-S Fab' Fragments
Anti-somatostatin IgG antibodies derived from rabbits were obtained from Purification Engineering, Inc. The antibodies were digested by papain, and the digest repurified on an S-Sepharose 4B affinity column. A total of 5.4 mg anti-S Fab' fragments were obtained (135 ml. 40 μg/ml of Fab').
Eighty 3-week old Cox SD rats were randomly assigned to four treatment groups. One group was designated the untreated control, one group the saline control, one the high Fab' group and the fourth was designated the low Fab' group. These last 3 designations are defined below:
Saline control--injected control with 0.5 ml saline (0.9% NaCl)
high Fab'--20 μg/injection in 0.5 ml saline
low Fab'--200 ng/injection in 0.5 ml. saline
After being quarantined for three days, intraperitoneal injections of 0.5 ml were given on days 1, 3 and 5 of each week for the duration of the 8 week study. Every two weeks one group of 5 animals from each of the 4 experimental conditions was weighed and sacrificed. Blood samples were taken and the sera were frozen and stored for future analysis. The bodies of the dead animals were inspected for unusual features.
The rats of each group were housed in a colony cage measuring 26"×20"×7" during the 8 week trial. The mean weights were taken at two-week intervals of all the rats present in each group. As noted above, in order to collect blood samples at each weighing date, five rats were sacrificed from each group every two weeks on the weighing day. Therefore, the number of rats represented by the mean varied from 20 rats at days 0 and 14 to 5 rats at day 56. All rats were fed standard laboratory rat chow and water, both ad lib. Lighting conditions were 16 hours of light and 8 hours of dark. The temperature fluctuated with ambient temperature (approximately 20° C.). Table A below shows the results of the mean weights. FIG. 1 shows the growth curve (mean weights) for the different groups. The percentage weight gain of the high Fab' group compared to the saline control group is listed in Table B below.
              TABLE A                                                     
______________________________________                                    
Mean Weight in Grams with Standard Deviation                              
     NontreatedSaline                                                     
Days ControlControl   High Fab'   Low Fab'                                
______________________________________                                    
 0    87.9 ± 8.3 86.8 ± 7.9                                         
                      89.5 ± 10.1                                      
                                  85.8 ± 8.4                           
14   177.5 ± 19.7 167.1 ± 23.7                                      
                      181.3 ± 19.8                                     
                                  168.0 ± 20.9                         
28   279.3 ± 24.4 257.2 ± 31.5                                      
                       267.0 ± 31.7*                                   
                                  243.6 ± 29.9                         
42   350.3 ± 27.9 323.1 ± 31.9                                      
                       362.1 ± 23.1*                                   
                                  313.4 ± 26.2                         
56   394.0 ± 22.6 373.0 ± 17.5                                      
                       403.4 ± 15.6*                                   
                                  359.8 ± 23.2                         
______________________________________                                    
 *Differ significantly from saline control by a twosided Dunnetts' test   
 (Gill, J.L., Animal and Medical Sciences Bol. I, pp. 183-185 (1978) Iowa 
 State University Press, Ames, Iowa), and by analysis of covariance       
 (Steele, R.G.D. and Torrie, J.H ., Principles and Procedures of          
 Statistics, McGrawHill Book Co. Inc. N.Y. (1960) ch. 3, pp. 43-44, ch. 4,
 pp. 57-58 and ch. 5, pp. 67-76).                                         

              TABLE B                                                     
______________________________________                                    
Gain Improvement of Fab' Group Compared                                   
to Saline Control                                                         
        % Gain of Fab' Group Compared to                                  
Day     Saline Control                                                    
______________________________________                                    
 0      102%                                                              
14      107.3%                                                            
28      105.7%                                                            
42      111.2%                                                            
56      109.6%                                                            
______________________________________
The levels of nitrogen excreted by an animal are a good indicator of anabolic activity. The levels of blood urea nitrogen (BUN) were measured to substantiate the weight gain results. FIG. 2 shows the mean blood urea-nitrogen levels for the different groups. As shown in FIG. 2, the BUN levels measured in the experimental and control groups suported the weight data. The group injected with high Fab' fragments showed significantly lower BUN levels than the other groups.
In similar operations, an increased growth rate is achieved in various species of birds and mammals, when they are administered growth promoting amounts of monoclonal and polyclonal Fab' fragments and whole antibodies from homologous species and monoclonal and polyclonal Fab' fragments from heterologous species.

Claims (10)

I claim:
1. A method of enhancing the rate of growth of an animal which comprises administering to said animal growth-enhancing amounts of antibodies against somatostatin.
2. The method of claim 1 wherein said antibodies are polyclonal antibodies.
3. The method of claim 1 wherein said antibodies are monolconal antibodies.
4. The method of claim 2 or 3 wherein the species of animal from which said antibodies are derived and the species of animal which will be administered said antibodies are homologous.
5. The method of claim 4 wherein whole antibodies are administered.
6. The method of claim 4 wherein Fab' fragments of said antibodies are administered.
7. The method of claim 2 or 3 wherein the species of animal from which said antibodies are derived and the species of animal which will be administered said antibodies are heterologous.
8. The method of claim 7 wherein Fab' fragments of said antibodies are administered.
9. The method of claim 1, 2 or 3 wherein the antibodies are administered by packaging a growth enhancing amount of the antibodies into slow-release delivery devices and implanting the devices in the animals to be immunized.
10. The method of claim 1, 2 or 3 wherein the antibodies are administered by injecting the animals with a solution comprising growth enhancing amounts of said antibodies.
US06/773,814 1985-09-09 1985-09-09 Method of promoting animal growth using antibodies against somatostatin Expired - Lifetime US4599229A (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US06/773,814 US4599229A (en) 1985-09-09 1985-09-09 Method of promoting animal growth using antibodies against somatostatin
DE86305234T DE3684211D1 (en) 1985-09-09 1986-07-07
EP86305234A EP0216454B1 (en) 1985-09-09 1986-07-07 Method of promoting animal growth
JP61158087A JPS6270321A (en) 1985-09-09 1986-07-07 Animal growth acceleration
AT86305234T ATE73350T1 (en) 1985-09-09 1986-07-07 METHOD OF ANIMAL GROWTH PROMOTION.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US06/773,814 US4599229A (en) 1985-09-09 1985-09-09 Method of promoting animal growth using antibodies against somatostatin

Publications (1)

Publication Number Publication Date
US4599229A true US4599229A (en) 1986-07-08

Family

ID=25099391

Family Applications (1)

Application Number Title Priority Date Filing Date
US06/773,814 Expired - Lifetime US4599229A (en) 1985-09-09 1985-09-09 Method of promoting animal growth using antibodies against somatostatin

Country Status (5)

Country Link
US (1) US4599229A (en)
EP (1) EP0216454B1 (en)
JP (1) JPS6270321A (en)
AT (1) ATE73350T1 (en)
DE (1) DE3684211D1 (en)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0270321A2 (en) * 1986-12-01 1988-06-08 The University Of British Columbia Monoclonal antibodies effective in promoting growth
US4929600A (en) * 1988-03-18 1990-05-29 University Of Deleware Endocrine manipulation to improve body composition of poultry
US5034229A (en) * 1988-12-13 1991-07-23 Alza Corporation Dispenser for increasing feed conversion of hog
US5037420A (en) * 1988-12-13 1991-08-06 Alza Corporation Delivery system comprising two sections for delivering somatotropin
US5057318A (en) * 1988-12-13 1991-10-15 Alza Corporation Delivery system for beneficial agent over a broad range of rates
US5059423A (en) * 1988-12-13 1991-10-22 Alza Corporation Delivery system comprising biocompatible beneficial agent formulation
US5110596A (en) * 1988-12-13 1992-05-05 Alza Corporation Delivery system comprising means for delivering agent to livestock
US5135523A (en) * 1988-12-13 1992-08-04 Alza Corporation Delivery system for administering agent to ruminants and swine
US5168102A (en) * 1988-03-18 1992-12-01 University Of Delaware Endocrine manipulation to improve body composition of poultry
US5174999A (en) * 1988-12-13 1992-12-29 Alza Corporation Delivery system comprising fluid ingress and drug egress
US5690952A (en) * 1995-06-07 1997-11-25 Judy A. Magruder et al. Implantable system for delivery of fluid-sensitive agents to animals
US5728088A (en) * 1988-12-13 1998-03-17 Alza Corporation Osmotic system for delivery of fluid-sensitive somatotropins to bovine animals
WO1999008708A2 (en) * 1997-08-21 1999-02-25 Dcv, Inc. Method and food product for increasing muscle protein and reducing fat in animals
US6165465A (en) * 1990-05-15 2000-12-26 American Cyanamid Company Immunologic enhancement of the somatogenic effect of somatotropin with an antibody
EP1149590A1 (en) * 1994-08-05 2001-10-31 Wisconsin Alumni Research Foundation Use of gut peptide antibodies to improve feed efficiency
US6818739B2 (en) 1999-12-03 2004-11-16 Ndsu Research Foundation Somatostatins
WO2018038803A1 (en) * 2016-08-26 2018-03-01 Nal Pharmaceutical Group Limited Compositions containing fusion protein of albumin and analogs thereof, methods for making and using the same
CN109641036A (en) * 2016-02-26 2019-04-16 安能泰制药有限公司 The composition of fusion protein comprising albumin and its analog, its preparation and application
US20210204529A1 (en) * 2020-01-07 2021-07-08 Iowa State University Research Foundation, Inc. Livestock animals with improved growth performance

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4172124A (en) * 1978-04-28 1979-10-23 The Wistar Institute Method of producing tumor antibodies
US4219467A (en) * 1977-12-27 1980-08-26 Istituto Sieroterapico & Vaccinogeno Toscano `SCLAVO` S.p.A. Method for the preparation of chorionic human somatomammotropin
JPS5616415A (en) * 1979-07-20 1981-02-17 Otsuka Pharmaceut Co Ltd Preparation of antibody
US4363877A (en) * 1977-09-23 1982-12-14 The Regents Of The University Of California Recombinant DNA transfer vectors
US4366246A (en) * 1977-11-08 1982-12-28 Genentech, Inc. Method for microbial polypeptide expression

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU85269A1 (en) * 1984-03-26 1985-10-14 Techland S A NOVEL SOMATOSTATIN COMPOUNDS, PROCESS FOR THEIR SYNTHESIS, PREPARATION FOR VETERINARY USE CONTAINING SAID COMPOUNDS AND PROCESS FOR THE TREATMENT OF ANIMALS
JPH08116415A (en) * 1994-10-14 1996-05-07 Fujitsu Ltd Facsimile equipment and facsimile data transmission and reception system

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4363877A (en) * 1977-09-23 1982-12-14 The Regents Of The University Of California Recombinant DNA transfer vectors
US4363877B1 (en) * 1977-09-23 1998-05-26 Univ California Recombinant dna transfer vectors
US4366246A (en) * 1977-11-08 1982-12-28 Genentech, Inc. Method for microbial polypeptide expression
US4219467A (en) * 1977-12-27 1980-08-26 Istituto Sieroterapico & Vaccinogeno Toscano `SCLAVO` S.p.A. Method for the preparation of chorionic human somatomammotropin
US4172124A (en) * 1978-04-28 1979-10-23 The Wistar Institute Method of producing tumor antibodies
JPS5616415A (en) * 1979-07-20 1981-02-17 Otsuka Pharmaceut Co Ltd Preparation of antibody

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Endocrinology, 106: 1027 1032 (1980), Varner et al. *
Endocrinology, 106: 1027-1032 (1980), Varner et al.

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0270321A2 (en) * 1986-12-01 1988-06-08 The University Of British Columbia Monoclonal antibodies effective in promoting growth
US4764475A (en) * 1986-12-01 1988-08-16 The University Of British Columbia Pancreas dependant immunoassay for determining subpopulations of monoclonal antibodies to somatostatin.
EP0270321A3 (en) * 1986-12-01 1989-08-16 The University Of British Columbia Monoclonal antibodies effective in promoting growth
US4929600A (en) * 1988-03-18 1990-05-29 University Of Deleware Endocrine manipulation to improve body composition of poultry
US5168102A (en) * 1988-03-18 1992-12-01 University Of Delaware Endocrine manipulation to improve body composition of poultry
US5110596A (en) * 1988-12-13 1992-05-05 Alza Corporation Delivery system comprising means for delivering agent to livestock
US5057318A (en) * 1988-12-13 1991-10-15 Alza Corporation Delivery system for beneficial agent over a broad range of rates
US5059423A (en) * 1988-12-13 1991-10-22 Alza Corporation Delivery system comprising biocompatible beneficial agent formulation
US5037420A (en) * 1988-12-13 1991-08-06 Alza Corporation Delivery system comprising two sections for delivering somatotropin
US5135523A (en) * 1988-12-13 1992-08-04 Alza Corporation Delivery system for administering agent to ruminants and swine
US5034229A (en) * 1988-12-13 1991-07-23 Alza Corporation Dispenser for increasing feed conversion of hog
US5174999A (en) * 1988-12-13 1992-12-29 Alza Corporation Delivery system comprising fluid ingress and drug egress
US5320616A (en) * 1988-12-13 1994-06-14 Alza Corporation Delivery system comprising first walled section and second walled section united by fusion, adhesion or telescopic engagement
US5630808A (en) * 1988-12-13 1997-05-20 Alza Corporation Delivery system comprising means for governing fluid into the system and for restricting fluid into the system
US6180129B1 (en) 1988-12-13 2001-01-30 Alza Corporation Polyurethane-containing delivery systems
US5714160A (en) * 1988-12-13 1998-02-03 Alza Corporation Delivery system comprising means for governing fluid ingress into the system
US5728088A (en) * 1988-12-13 1998-03-17 Alza Corporation Osmotic system for delivery of fluid-sensitive somatotropins to bovine animals
US6165465A (en) * 1990-05-15 2000-12-26 American Cyanamid Company Immunologic enhancement of the somatogenic effect of somatotropin with an antibody
EP1149590A1 (en) * 1994-08-05 2001-10-31 Wisconsin Alumni Research Foundation Use of gut peptide antibodies to improve feed efficiency
US5871770A (en) * 1995-06-07 1999-02-16 Alza Corporation Implantable system for delivery of fluid-sensitive agents to animals
US5690952A (en) * 1995-06-07 1997-11-25 Judy A. Magruder et al. Implantable system for delivery of fluid-sensitive agents to animals
WO1999008708A2 (en) * 1997-08-21 1999-02-25 Dcv, Inc. Method and food product for increasing muscle protein and reducing fat in animals
WO1999008708A3 (en) * 1997-08-21 1999-04-15 Dcv Inc Method and food product for increasing muscle protein and reducing fat in animals
US6086878A (en) * 1997-08-21 2000-07-11 Dcv, Inc. Method of increasing muscle protein and reducing fat in animals
US6818739B2 (en) 1999-12-03 2004-11-16 Ndsu Research Foundation Somatostatins
CN109641036A (en) * 2016-02-26 2019-04-16 安能泰制药有限公司 The composition of fusion protein comprising albumin and its analog, its preparation and application
WO2018038803A1 (en) * 2016-08-26 2018-03-01 Nal Pharmaceutical Group Limited Compositions containing fusion protein of albumin and analogs thereof, methods for making and using the same
US20210204529A1 (en) * 2020-01-07 2021-07-08 Iowa State University Research Foundation, Inc. Livestock animals with improved growth performance
US11793179B2 (en) * 2020-01-07 2023-10-24 Iowa State University Research Foundation, Inc. Livestock animals with improved growth performance

Also Published As

Publication number Publication date
ATE73350T1 (en) 1992-03-15
DE3684211D1 (en) 1992-04-16
JPS6270321A (en) 1987-03-31
EP0216454A2 (en) 1987-04-01
EP0216454B1 (en) 1992-03-11
EP0216454A3 (en) 1989-01-11

Similar Documents

Publication Publication Date Title
US4599229A (en) Method of promoting animal growth using antibodies against somatostatin
CA2047717C (en) Monoclonal antibodies for small moieties, methods therefor
Nilsson et al. Immunization of mice and rabbits by intrasplenic deposition of nanogram quantities of protein attached to Sepharose beads or nitrocellulose paper strips
US4504586A (en) Hybridoma tumor cell lines and their monoclonal antibodies to human colony stimulating factor subclass number 1
EP0014519A2 (en) Cell lines, process for preparing them and process for producing antibodies
SK635290A3 (en) Polypeptide, subsequences thereof and their use
CA1240939A (en) Monoclonal antibodies to human immune interferon
EP0265384A2 (en) Monoclonal antibodies to a colony stimulating factor
CA1259923A (en) Physiologically active compositions
CA1307218C (en) Onco-fetal specific monoclonal antibodies methods of preparation and use
EP0168907B1 (en) Monoclonal antibodies recognizing l-thyroxine
Stuart et al. The production of monoclonal antibodies to human chorionic gonadotrophin and its subunits
US4764475A (en) Pancreas dependant immunoassay for determining subpopulations of monoclonal antibodies to somatostatin.
EP0173712A1 (en) Immunization by immunogenic implant
CN1195069C (en) Process for preparing human follicle-stimualting hormone beta subunit monoclonal antibody
EP0328248A2 (en) Monoclonal antibodies against a follicle-stimulating hormone
Trenkle et al. An immunological investigation of porcine pituitary growth hormone
Garvey et al. The in vivo stability of antibody
De Pablo et al. Handbook of endocrine research techniques
US6165465A (en) Immunologic enhancement of the somatogenic effect of somatotropin with an antibody
RU2059720C1 (en) Strain of hybrid cultured murine cells mus musculus l used for preparing monoclonal antibodies to the human thyrotropic hormone
RU2059721C1 (en) Strain of hybrid cultured murine cells mus musculus l used for preparing monoclonal antibodies to the human thyrotropic hormone
SU1671688A1 (en) Strain of hybridous cultured mammalian cells mus musculus l - a producer of monoclonal antibodies for glycopproteid e1 of equine east encephalitis virus
CA1288341C (en) Physiologically active compositions
Maezawa et al. Long-term observation of passive Heymann nephritis

Legal Events

Date Code Title Description
AS Assignment

Owner name: INTERNATIONAL MINERALS & CHEMICAL CORPORATION, A C

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:MACCECCHINI, MARIA-LUISA;REEL/FRAME:004459/0311

Effective date: 19850830

STCF Information on status: patent grant

Free format text: PATENTED CASE

CC Certificate of correction
FPAY Fee payment

Year of fee payment: 4

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12

AS Assignment

Owner name: SCHERING-PLOUGH ANIMAL HEALTH CORPORATION, NEW JER

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MALLINCKRODT, INC.;REEL/FRAME:008886/0806

Effective date: 19970629